Using heat shock proteins to increase immune response

Abstract

The present invention provides for a method of using heat shock proteins (HSPs) to amplify the immune response initiated by a vaccine. HSPs can be introduced into a subject before, concurrently, or after the administration of a vaccine. The HSPs can also be used to activate antigen presenting cells which are then introduced into a subject in conjunction with a vaccine. The HSPs used in the methods of the invention can be unbound or can be covalently or noncovalently bound to a peptide that is unrelated to the vaccine. The subject is preferably mammalian, and most preferably human. It is shown by way of example herein that HSPs induces secretion of cytokines and surface expression of antigen-presenting and co-stimulatory molecules. The invention also encompasses methods of treatment and prevention of cancer and infectious diseases in a subject.

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         2 . A method of inducing an immune response by a vaccine composition in a subject comprising the steps of: 
 (a) administering to the subject a heat shock protein preparation; and    (b) administering to the subject a vaccine composition comprising a component against which an immune response is desired to be induced, the vaccine composition being in an amount that is sub-immunogenic for the component in the absence of step (a),    such that an immune response to the component is induced in the subject, and wherein the heat shock protein preparation does not display the immunogenicity of the component.    
     
     
         3 . A method of treating or preventing an infectious disease in a subject comprising the steps of: 
 (a) administering to the subject a vaccine composition comprising a component that displays the antigenicity of an infectious agent that causes the infectious disease; and    (b) administering to the subject an amount of a heat shock protein preparation effective in combination with step (a) to induce or increase an immune response to the component in the subject, wherein the heat shock protein preparation does not display the immunogenicity of the component.    
     
     
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         8 . The method according to  claim 3  wherein the heat shock protein preparation comprises a heat shock protein selected from the group consisting of hsp70, hsp90, gp96, calreticulin, and a combination thereof.  
     
     
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         12 . The method according to  claim 3  wherein the heat shock protein preparation comprises heat shock protein-peptide complexes.  
     
     
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         16 . The method according to  claim 3  wherein the heat shock protein preparation comprises purified heat shock proteins.  
     
     
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         20 . The method according to  claim 3  wherein the heat shock protein preparation comprises heat shock protein-peptide complexes and purified heat shock proteins.  
     
     
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         24 . The method according to  claim 3  wherein the subject is human and the heat shock protein preparation comprises mammalian heat shock proteins.  
     
     
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         26 . The method according to  claim 3 ,  8 ,  12 ,  16 ,  20 , or  24  wherein the heat shock protein is administered before the administration of the vaccine composition.  
     
     
         27 . The method according to  claim 3 ,  8 ,  12 ,  16 ,  20 , or  24  wherein the heat shock protein preparation is administered concurrently with the administration of the vaccine composition.  
     
     
         28 . The method according to  claim 3 ,  8 ,  12 ,  16 ,  20 , or  24  wherein the heat shock protein is preparation administered after the administration of the vaccine composition.  
     
     
         29 . The method according to  claim 8  wherein the heat shock protein preparation is administered before the administration of the vaccine composition.  
     
     
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         41 . The method according to  claim 20  wherein the heat shock protein preparation and the vaccine composition are both administered on the same day.  
     
     
         42 . The method according to  claim 24  wherein the vaccine composition is a live vaccine, an attenuated vaccine, a subunit vaccine, a DNA vaccine, or a RNA vaccine.  
     
     
         43 . The method according to  claim 3  wherein the infectious disease is selected from the group consisting of hepatitis A virus, hepatitis B virus; hepatitis C virus, influenza, varicella, adenovirus, herpes simplex I virus, herpes simplex II virus, rinderpest, rhinovirus, ECHO virus, rotavirus, respiratory syncytial virus, papilloma virus, papova virus, cytomegalovirus, echinovirus, arbovirus, hantavirus, coxsackie virus, mumps virus, measles virus, rubella virus, polio virus, human immunodeficiency virus type I (HIV-I), human immunodeficiency virus type II (HIV-II), mycobacteria,  rickettsia, mycoplasma, neisseria, legionella, leishmania , kokzidioa,  trypanosoma  and  chlamydia.    
     
     
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